Topical Ciprofloxacin compositions

Abstract

Embodiments of the invention provide pharmaceutical compositions of ciprofloxacin formulated for topical application to a body surface and for having at least localized antibacterial activity. In some embodiments, the compositions are further formulated for localized anti-inflammatory activity, anti-fungal activity, anti-viral activity, or combinations thereof. Such compositions possess a therapeutically effective amount of a non-betaine form ciprofloxacin (e.g., ciprofloxacin hydrochloride monohydrate); one of a pH adjusting agent and a preservative; water; and a pH from about 5.5 to about 10. In some embodiments, such compositions may be free or free of added skin permeation enhancer and/or contain a betaine form ciprofloxacin.

What is claimed is: 
     
       1. A pharmaceutical composition formulated for: a. topical application to a body surface, and b. antibacterial activity localized to the body surface, the pharmaceutical composition consisting essentially of:
 a therapeutically effective amount of a non-betaine form ciprofloxacin; 
 at least one member selected from the group consisting of a pH adjusting agent and a preservative; 
 water; and 
 a pH of from more than 6 to about 8.5, 
 
       wherein:
 more than 10% of the non-betaine form ciprofloxacin is in the pharmaceutical composition in suspended form; 
 the body surface is: at least one member of the group consisting of a dermal surface, an ophthalmic surface, a mucosal surface, and a fingernail surface, and/or in at least one member selected from the group consisting of an ear canal, an oral cavity, a pharyngeal cavity, a nasal cavity, a pulmonary cavity, a vaginal cavity, and a rectal cavity; and 
 the pharmaceutical composition exhibits a more rapid onset of antibacterial activity than a comparator formulation that differs from the pharmaceutical composition by having: a pH of about 4.5 and 5% or less of the non-betaine form ciprofloxacin in suspension. 
 
     
     
       2. The pharmaceutical composition of  claim 1 , wherein:
 the non-betaine form ciprofloxacin is a ciprofloxacin hydrochloride and the therapeutically effective amount of the ciprofloxacin hydrochloride is from about 0.05% w/w to about 20% w/w of the composition; 
 the pH adjusting agent, when present in the composition, is selected from the group consisting of a hydrochloric acid, a sulfuric acid, a phosphoric acid, a sodium hydroxide, a potassium hydroxide, a calcium hydroxide, a magnesium hydroxide, an ethanolamine, and a combination thereof; and 
 the preservative, when present in the composition, is: in an amount ranging from about 0.001% w/w to about 2.5% w/w of the composition and is selected from the group consisting of a benzalkonium chloride, a lauralkonium chloride, a cetrimonium, a chlorobutanol, a methyl paraben, a propyl paraben, a phenylethyl alcohol, a borate, a sorbate, and a combination thereof. 
 
     
     
       3. The pharmaceutical composition of  claim 2 , further consisting essentially of at least one member selected from the group consisting of:
 an amount of an osmolality adjusting agent sufficient to provide the composition with an osmotic pressure of from about 100 mOsM to about 600 mOsM, the osmolality adjusting agent selected from the group consisting of a glycerol, a mannitol, a xylitol, a sorbitol, a dextrose, a glucose, a maltose, a trehalose, a sucrose, a cyclodextrin, a propylene glycol a, sodium chloride, a potassium chloride, a calcium chloride, a magnesium chloride, a sodium bisulfite, a sodium sulfite, a sodium sulfate, a sodium bicarbonate, a sodium carbonate, a sodium thiosulfate, a potassium acetate, a sodium acetate, a magnesium sulfate, a disodium hydrogen phosphate, a sodium dihydrogen phosphate, a potassium dihydrogen phosphate, and a combination thereof; 
 from about 0.01% w/w to about 5% w/w of a viscosity building agent selected from the group consisting of a polyethylene glycol, a polyvinyl alcohol, a polyvinyl pyrrolidone, a polyvinyl alcohol, a methylcellulose, a hydroxyethylcellulose, a hydroxypropylcellulose, a guar gum, a hydroxypropyl guar gum, a gum arabic, a karaya gum, a xanthan gum, an agar, an alginic acid, a dextran, a heparin, a hyaluronic acid, a chondroitin sulfate, a starch, a chitin, a carrageenan, a polyacrylate, a casein, a gelatin, a collagen, a pectin, an elastin, and a combination thereof; 
 from about 0.01% w/w to about 5% w/w of a buffer selected from the group consisting of a phosphate buffer, a citrate buffer, an acetate buffer, a carbonate buffer, a succinate buffer, a bicine buffer, a TRIS buffer, a tricine buffer, a TAPS 0 buffer, a HEPES buffer, a TES buffer, a MOPS buffer, a PIPES buffer, a cacodylate buffer, a MES buffer, and a combination thereof; 
 from about 0.001% w/w to about 5% w/w of a chelating agent selected from the group consisting of a adeferoxamine, an ethylenediaminetetraacetic acid, an ethyleneglycoltetraacetic acid, and a combination thereof; and 
 from about 0.01% w/w to about 5% w/w of a surfactant selected from the group consisting of a sorbitan, a polysorbate, a poloxamer, a sodium lauryl sulfate, a tyloxapol, and a combination thereof. 
 
     
     
       4. The pharmaceutical composition of  claim 3 , further consisting essentially of:
 from about 0.25% w/w to about 5% w/w of the ciprofloxacin hydrochloride; 
 from about 0.005% w/w to about 1.0% w/w of the preservative selected from the group consisting of the benzalkonium chloride and the borate; 
 from about 0.001% w/w to about 1.5% w/w the sodium chloride osmolality adjusting agent; 
 from about 0.1% w/w to about 2.5% w/w of the hydroxyethylcellulose viscosity building agent 
 from about 0.005% w/w to about 0.5% w/w of the ethylenediaminetetraacetic chelating agent; 
 
       from about 0.005% w/w to about 1.0% w/w of the tyloxapol surfactant, and wherein the pharmaceutical composition exhibits the more rapid onset of antibacterial activity against a bacteria selected from the group consisting of  Haemophilus influenza, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus, Serrata marcescens , and  Klebisiella pneumoniae.    
     
     
       5. The pharmaceutical composition of  claim 3 , wherein the composition consists essentially of:
 about 0.35% w/w of the non-betaine form ciprofloxacin hydrochloride monohydrate; 
 about 0.01% w/w of the benzalkonium chloride 
 about 0.06% w/w of the boric acid; 
 about 0.53% w/w of the sodium chloride; 
 about 0.2% w/w of the hydroxyethylcellulose; 
 about 0.01% w/w of the sodium acetate; 
 about 0.1% w/w of the acetic acid; 
 about 0.01% w/w of the ethylenediaminetetraacetic acid; and 
 about 0.05% w/w of the tyloxapol. 
 
     
     
       6. The pharmaceutical composition of  claim 1 , wherein more than 50% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       7. The pharmaceutical composition of  claim 6 , wherein more than 60% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       8. The pharmaceutical composition of  claim 7 , wherein more than 70% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       9. The pharmaceutical composition of  claim 8 , wherein more than 80% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       10. The pharmaceutical composition of  claim 3 , wherein more than 50% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       11. The pharmaceutical composition of  claim 10 , wherein more than 60% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       12. The pharmaceutical composition of  claim 11 , wherein more than 70% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       13. The pharmaceutical composition of  claim 12 , wherein more than 80% of the non-betaine form ciprofloxacin is in suspended form. 
     
     
       14. The pharmaceutical composition of  claim 4 , further consisting essentially of from 0.01% w/w to 1.5% w/w of a corticosteroid drug. 
     
     
       15. The pharmaceutical composition of  claim 4 , further consisting essentially of from 0.01% w/w to 1.5% w/w of a decongestant drug. 
     
     
       16. The pharmaceutical composition of  claim 4 , further consisting essentially of from 0.01% w/w to 1.5% w/w of a topical anesthetic.